Crystal of monohydrate of heterocyclic bis(phosphonic acid) derivative

Abstract

Crystal D or E of 1-hydroxy-2-(imidazo[1,2-a]pyridin-3-yl)ethane -1,1-bis(phosphonic acid) monohydrate having specified lattice spacing and relative intensity in the powder X-ray diffraction spectrum obtained by using Cu-Kα radiation and a dehydration peak temperature of 135° to 149° C. or 160° to 170° C. according to TG-DSC thermogravimetric analysis; and to a solid pharmaceutical preparation containing the same. The crystals are useful for producing a stable solid pharmaceutical preparation of the above compound which has an excellent drug efficacy for diseases wherein increased bone resorption participates, such as osteoporosis.

We claim: 
     
       1. A crystal selected from the group consisting of crystals D and E of 1-hydroxy-2-(imidazo[1,2-a]pyridin-3-yl)ethane-1,1-bis(phosphonic acid) monohydrate having the following physicochemical properties (1) crystal D: has the lattice spacing and relative intensity shown in Table 1 in the powder X-ray diffraction spectrum obtained by using Cu-Kα ray and a dehydration peak temperature of 135° to 149° C. according to TG-DSC thermogravimetric analysis                 TABLE 1                                                     
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Lattice spacing (Å)                                                   
                Relative intensity                                        
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8.77 ± 0.10  medium                                                    
6.50 ± 0.05  "                                                         
5.73 ± 0.03  "                                                         
5.48 ± 0.04  strong                                                    
5.21 ± 0.03  medium                                                    
4.86 ± 0.03  "                                                         
4.73 ± 0.03  strong                                                    
4.42 ± 0.03  medium                                                    
4.37 ± 0.03  "                                                         
3.38 ± 0.02  slightly strong                                           
3.23 ± 0.02  strong                                                    
3.19 ± 0.02  medium                                                    
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       (2) Crystal E: has the lattice spacing and relative intensity shown in the above Table 1 in the powder X-ray diffraction spectrum obtained by using Cu-Kα ray and a dehydration peak temperature of 160° to 170° C. according to TG-DSC thermogravimetric analysis.   
     
     
       2. A crystal of claim 1, which is crystal D of the 1-hydroxy-2-(imidazo[1,2-a]pyridin-3-yl)ethane-1,1-bis(phosphonic acid) monohydrate. 
     
     
       3. A crystal of claim 1, which is crystal E of the 1-hydroxy-2-(imidazo[1,2-a]pyridin-3-yl)ethane-1,1-bis(phosphonic acid) monohydrate. 
     
     
       4. A solid pharmaceutical preparation which comprises a crystal selected from the group consisting of crystals D and E of the 1-hydroxy-2-(imidazo[1,2-a]pyridin-3-yl)ethane-1,1-bis(phosphonic acid) monohydrate of claim 1 and a carrier for solid pharmaceutical preparation use. 
     
     
       5. The solid pharmaceutical preparation according to claim 4, wherein said solid pharmaceutical preparation contains crystal D of the 1-hydroxy-2-(imidazo[1,2-a]pyridin-3-yl)ethane-1,1-bis(phosphonic acid) monohydrate. 
     
     
       6. The solid pharmaceutical preparation according to claim 4, which is a preparation for preventing and/or treating diseases in which increased bone resorption participates. 
     
     
       7. The solid pharmaceutical preparation according to claim 6, which is a preparation for preventing and/or treating osteoporosis. 
     
     
       8. A method for treating osteoporosis in a host inflicted with such a condition which comprises administering to said host, an osteoporosis inhibiting amount of the pharmaceutical preparation of claim 4. 
     
     
       9. A method for treating osteoporosis in a host inflicted with such a condition which comprises administering to said host, an osteoporosis inhibiting amount of the pharmaceutical preparation of claim 5.